Tetrahydrofuran → HCID 57388934, compound

HRID 2406921Notes

Reaction equation

HRID 2406921 reaction equation
[CH3:1][CH:2]([CH3:37])[CH2:3][C@@H:4]([NH:21][C:22]1[CH:36]=[CH:35][C:25]([C:26]([NH:28][CH2:29][CH2:30][C:31]([O:33]C)=[O:32])=[O:27])=[CH:24][N:23]=1)[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1.O1CCCC1.[OH-].[Na+]>CO>[CH3:1][CH:2]([CH3:37])[CH2:3][C@@H:4]([NH:21][C:22]1[CH:36]=[CH:35][C:25]([C:26]([NH:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[O:27])=[CH:24][N:23]=1)[C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:15][CH:16]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67980809HCID 67980809, compound

Product 1

HCID 57388934HCID 57388934, compoundYield 504.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A round bottom flask was charged with (R)-methyl 3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinamido)propanoate (6.26 g, 10.2 mmol), tetrahydrofuran (60 mL) and methanol (60 mL). 1.0N NaOH (18.3 mL, 18.3 mmol) was added and the resulting solution was stirred at room temperature for 15 min. The organic solvents were removed under reduced pressure and the resulting crude was diluted with water. 10% Citric acid was added to acidify the solution to pH˜3. A white precipitate formed. After stirring for 30 minutes at room temperature, the solid was filtered off and dried under vacuum. Purification by column chromatography (0-10% methanol/dichloromethane) provided (R)-3-(6-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)nicotinamido)propanoic acid (25.7 g, 76.4%) as a white solid. 1H NMR (400 MHz, (CD3)2SO, δ): 0.91 (d, J=6.44 Hz, 3 H) 0.95 (d, J=6.44 Hz, 3 H) 1.48-1.59 (m, 1 H) 1.61-1.71 (m, 1 H) 1.72-1.82 (m, 1 H) 2.44 (t, J=7.12 Hz, 2 H) 3.34-3.42 (m, 2 H) 5.10 (br. s., 1 H) 6.52 (d, J=8.78 Hz, 1 H) 7.46-7.51 (m, 2 H) 7.57 (d, J=8.19 Hz, 1 H) 7.63-7.69 (m, 2 H) 7.74 (dd, J=8.88, 2.44 Hz, 1 H) 7.76-7.81 (m, 2 H) 7.83-7.89 (m, 2 H) 8.15 (t, J=5.46 Hz, 1 H) 8.40 (d, J=2.34 Hz, 1 H) 12.18 (br. s., 1 H). MS (M+1): 500.4.

Workup

  1. customThe organic solvents were removed under reduced pressure
  2. additionthe resulting crude was diluted with water
  3. addition10% Citric acid was added
  4. customA white precipitate formed
  5. stirringAfter stirring for 30 minutes at room temperature
  6. filtrationthe solid was filtered off
  7. customdried under vacuum
  8. customPurification by column chromatography (0-10% methanol/dichloromethane)

Sources & evidence

ORD record
ord-436f5e6fc09e4cc59229e9bed3271f51
Source dataset
uspto-grants-2014_08
Patent number
US08809342B2

Reaction notes

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